NZ517426A - Phosphate mimics and methods of treatment using phosphatase inhibitors - Google Patents
Phosphate mimics and methods of treatment using phosphatase inhibitorsInfo
- Publication number
- NZ517426A NZ517426A NZ517426A NZ51742600A NZ517426A NZ 517426 A NZ517426 A NZ 517426A NZ 517426 A NZ517426 A NZ 517426A NZ 51742600 A NZ51742600 A NZ 51742600A NZ 517426 A NZ517426 A NZ 517426A
- Authority
- NZ
- New Zealand
- Prior art keywords
- trifluoromethanesulfonyl
- phenyl
- bis
- phenoxy
- methyl
- Prior art date
Links
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 title claims description 45
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 title claims description 45
- 238000000034 method Methods 0.000 title description 76
- 238000011282 treatment Methods 0.000 title description 18
- 239000003112 inhibitor Substances 0.000 title description 12
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- 230000000694 effects Effects 0.000 claims abstract description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 60
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 claims abstract description 45
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 claims abstract description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 29
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 28
- -1 N-amido Chemical group 0.000 claims description 124
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 111
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 86
- 125000003118 aryl group Chemical group 0.000 claims description 86
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 84
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 75
- 229910052757 nitrogen Inorganic materials 0.000 claims description 69
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 68
- 125000003545 alkoxy group Chemical group 0.000 claims description 59
- 229910052799 carbon Inorganic materials 0.000 claims description 59
- 229910052760 oxygen Inorganic materials 0.000 claims description 58
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 57
- 230000019491 signal transduction Effects 0.000 claims description 57
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 56
- 125000004429 atom Chemical group 0.000 claims description 54
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 claims description 50
- 210000004027 cell Anatomy 0.000 claims description 49
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 claims description 47
- 229910052717 sulfur Inorganic materials 0.000 claims description 45
- 150000003536 tetrazoles Chemical class 0.000 claims description 45
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 43
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 43
- 102000004190 Enzymes Human genes 0.000 claims description 43
- 108090000790 Enzymes Proteins 0.000 claims description 43
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 42
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 claims description 42
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 claims description 42
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 40
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 40
- 125000001188 haloalkyl group Chemical group 0.000 claims description 40
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 40
- 239000001301 oxygen Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 39
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 38
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 38
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 38
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 38
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 36
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 36
- 239000005711 Benzoic acid Substances 0.000 claims description 36
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 36
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 36
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 36
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 36
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 36
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 35
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 35
- 125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
- 239000011593 sulfur Substances 0.000 claims description 35
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 33
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 31
- 125000002947 alkylene group Chemical group 0.000 claims description 30
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 28
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 201000011510 cancer Diseases 0.000 claims description 28
- 239000012453 solvate Substances 0.000 claims description 28
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 27
- 125000005263 alkylenediamine group Chemical group 0.000 claims description 27
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 27
- 150000003852 triazoles Chemical class 0.000 claims description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 25
- 108090000623 proteins and genes Proteins 0.000 claims description 25
- 125000004104 aryloxy group Chemical group 0.000 claims description 24
- 125000005001 aminoaryl group Chemical group 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims description 20
- 108091000080 Phosphotransferase Proteins 0.000 claims description 19
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 19
- 125000004450 alkenylene group Chemical group 0.000 claims description 19
- 125000004419 alkynylene group Chemical group 0.000 claims description 19
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 102000020233 phosphotransferase Human genes 0.000 claims description 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 19
- 229930192474 thiophene Natural products 0.000 claims description 19
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 18
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 18
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 18
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 claims description 18
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 18
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 18
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 18
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 18
- 125000005354 acylalkyl group Chemical group 0.000 claims description 18
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 18
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 18
- 125000005248 alkyl aryloxy group Chemical group 0.000 claims description 18
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 18
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 18
- 125000005122 aminoalkylamino group Chemical group 0.000 claims description 18
- 125000001769 aryl amino group Chemical group 0.000 claims description 18
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 18
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 18
- 125000005142 aryl oxy sulfonyl group Chemical group 0.000 claims description 18
- 230000027455 binding Effects 0.000 claims description 18
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 claims description 18
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 18
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 18
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 18
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 18
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 18
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 18
- KJKJUXGEMYCCJN-UHFFFAOYSA-N parathiazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CCN1CCCC1 KJKJUXGEMYCCJN-UHFFFAOYSA-N 0.000 claims description 18
- 229950011293 parathiazine Drugs 0.000 claims description 18
- 229950000688 phenothiazine Drugs 0.000 claims description 18
- 229960005141 piperazine Drugs 0.000 claims description 18
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 18
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 18
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 17
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 16
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 16
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 15
- 125000005631 S-sulfonamido group Chemical group 0.000 claims description 15
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 15
- 206010012601 diabetes mellitus Diseases 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 13
- ILDYBXVKXUBSQV-UHFFFAOYSA-N 2-[2-methyl-5-(trifluoromethylsulfonylamino)indol-1-yl]acetic acid Chemical compound FC(F)(F)S(=O)(=O)NC1=CC=C2N(CC(O)=O)C(C)=CC2=C1 ILDYBXVKXUBSQV-UHFFFAOYSA-N 0.000 claims description 12
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 11
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 11
- WJXRZFKTJXEJBK-UHFFFAOYSA-N methyl 4-[2-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]ethoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OCCOC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O WJXRZFKTJXEJBK-UHFFFAOYSA-N 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 11
- MTKGHXJALPACFQ-UHFFFAOYSA-N 4-[3-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]phenoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=CC(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)=C1 MTKGHXJALPACFQ-UHFFFAOYSA-N 0.000 claims description 10
- 235000010233 benzoic acid Nutrition 0.000 claims description 10
- PTTAYMXRNRMWAD-UHFFFAOYSA-N 1-(trifluoromethylsulfonyl)-4-[[4-(trifluoromethylsulfonyl)phenyl]methoxymethyl]benzene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1COCC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 PTTAYMXRNRMWAD-UHFFFAOYSA-N 0.000 claims description 9
- WAFAMMJKOMRAGL-UHFFFAOYSA-N 4-[3-[4-(trifluoromethylsulfonyl)phenoxy]phenoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=CC(OC=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)=C1 WAFAMMJKOMRAGL-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 230000004715 cellular signal transduction Effects 0.000 claims description 9
- QLBBSWVGCKBKNV-UHFFFAOYSA-N ethyl 2-[4-[4-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]phenyl]sulfonylphenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O QLBBSWVGCKBKNV-UHFFFAOYSA-N 0.000 claims description 9
- AYEDGAMSFLAABT-UHFFFAOYSA-N methyl 3,5-bis[4-(trifluoromethylsulfonyl)phenoxy]benzoate Chemical compound C=1C(OC=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)=CC(C(=O)OC)=CC=1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 AYEDGAMSFLAABT-UHFFFAOYSA-N 0.000 claims description 9
- XPBHMPWZWZVZHM-UHFFFAOYSA-N n-[[4-(trifluoromethylsulfonyl)phenyl]methyl]benzamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CNC(=O)C1=CC=CC=C1 XPBHMPWZWZVZHM-UHFFFAOYSA-N 0.000 claims description 9
- UYRZNNVCKGHQCX-UHFFFAOYSA-N 2-[2-[2-oxo-2-[3-(trifluoromethylsulfonyl)anilino]ethyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1CC(=O)NC1=CC=CC(S(=O)(=O)C(F)(F)F)=C1 UYRZNNVCKGHQCX-UHFFFAOYSA-N 0.000 claims description 8
- UKFSDFOCQZURJK-UHFFFAOYSA-N 3,5-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]benzamide Chemical compound C=1C(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)=CC(C(=O)N)=CC=1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O UKFSDFOCQZURJK-UHFFFAOYSA-N 0.000 claims description 8
- CBVWDVQMSDZXHH-UHFFFAOYSA-N 3,5-bis[4-(trifluoromethylsulfonyl)phenoxy]benzoic acid Chemical compound C=1C(OC=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)=CC(C(=O)O)=CC=1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 CBVWDVQMSDZXHH-UHFFFAOYSA-N 0.000 claims description 8
- JVMLTDTXYJCAOI-UHFFFAOYSA-N 4-[2,3-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propyl]morpholine Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1OCC(OC=1C(=CC(=CC=1)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)CN1CCOCC1 JVMLTDTXYJCAOI-UHFFFAOYSA-N 0.000 claims description 8
- NAZQHTPGLRDREQ-UHFFFAOYSA-N 4-[2-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]ethoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCCOC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O NAZQHTPGLRDREQ-UHFFFAOYSA-N 0.000 claims description 8
- AYRFMXQCOZEZGO-UHFFFAOYSA-N 4-[[2-hydroxy-3-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propyl]amino]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NCC(O)COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O AYRFMXQCOZEZGO-UHFFFAOYSA-N 0.000 claims description 8
- 208000001132 Osteoporosis Diseases 0.000 claims description 8
- 102000001253 Protein Kinase Human genes 0.000 claims description 8
- 238000003556 assay Methods 0.000 claims description 8
- 239000001273 butane Substances 0.000 claims description 8
- PSXXXDGBBSMMJZ-UHFFFAOYSA-N diethyl 2,5-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]benzene-1,4-dicarboxylate Chemical compound CCOC(=O)C=1C=C(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)C(C(=O)OCC)=CC=1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O PSXXXDGBBSMMJZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000002255 enzymatic effect Effects 0.000 claims description 8
- YYCONNQHASZKBK-UHFFFAOYSA-N methyl 2-[3,5-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]phenyl]acetate Chemical compound C=1C(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)=CC(CC(=O)OC)=CC=1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O YYCONNQHASZKBK-UHFFFAOYSA-N 0.000 claims description 8
- WFJJBULLQRPHIG-UHFFFAOYSA-N n-[2,3-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propyl]-4-nitroaniline Chemical compound C1=CC([N+](=O)[O-])=CC=C1NCC(OC=1C(=CC(=CC=1)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O WFJJBULLQRPHIG-UHFFFAOYSA-N 0.000 claims description 8
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 8
- 239000001294 propane Substances 0.000 claims description 8
- KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 claims description 8
- XYZIXFRCBYTCNC-UHFFFAOYSA-N 1-(trifluoromethylsulfonyl)-4-[[4-(trifluoromethylsulfonyl)phenoxy]methyl]benzene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 XYZIXFRCBYTCNC-UHFFFAOYSA-N 0.000 claims description 7
- TWQHRQGRHYCMTB-UHFFFAOYSA-N 2-[4-[4-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]phenyl]sulfonylphenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O TWQHRQGRHYCMTB-UHFFFAOYSA-N 0.000 claims description 7
- ZCMRRPGKZUKXPN-UHFFFAOYSA-N 3-[[2-[2-methyl-5-(trifluoromethylsulfonylamino)indol-1-yl]acetyl]amino]benzoic acid Chemical compound CC1=CC2=CC(NS(=O)(=O)C(F)(F)F)=CC=C2N1CC(=O)NC1=CC=CC(C(O)=O)=C1 ZCMRRPGKZUKXPN-UHFFFAOYSA-N 0.000 claims description 7
- CBXSDAAKCABFGJ-UHFFFAOYSA-N 4-[2,3-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propylamino]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NCC(OC=1C(=CC(=CC=1)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O CBXSDAAKCABFGJ-UHFFFAOYSA-N 0.000 claims description 7
- USPHOEVNPWLSKU-UHFFFAOYSA-N 4-[[2-[2-methyl-5-(trifluoromethylsulfonylamino)indol-1-yl]acetyl]amino]benzoic acid Chemical compound CC1=CC2=CC(NS(=O)(=O)C(F)(F)F)=CC=C2N1CC(=O)NC1=CC=C(C(O)=O)C=C1 USPHOEVNPWLSKU-UHFFFAOYSA-N 0.000 claims description 7
- RTSWXCWOWFBALQ-UHFFFAOYSA-N 6-[[methyl(trifluoromethylsulfonyl)amino]methyl]naphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(CN(C)S(=O)(=O)C(F)(F)F)=CC=C21 RTSWXCWOWFBALQ-UHFFFAOYSA-N 0.000 claims description 7
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 7
- 150000001408 amides Chemical group 0.000 claims description 7
- MLDQYTPYKVGMNI-UHFFFAOYSA-N diethyl 2-hydroxy-5-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]benzene-1,4-dicarboxylate Chemical compound C1=C(O)C(C(=O)OCC)=CC(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)=C1C(=O)OCC MLDQYTPYKVGMNI-UHFFFAOYSA-N 0.000 claims description 7
- KZGCCWAGYZGCOH-UHFFFAOYSA-N ethyl 2-[4-[4-[4-(trifluoromethylsulfonyl)phenoxy]phenyl]sulfonylphenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 KZGCCWAGYZGCOH-UHFFFAOYSA-N 0.000 claims description 7
- YIRKNERBPAUMBW-UHFFFAOYSA-N ethyl 2-[[2-[acetyl(cyclopropyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetate Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=CC=1C(C(=O)NCC(=O)OCC)N(C(C)=O)C1CC1 YIRKNERBPAUMBW-UHFFFAOYSA-N 0.000 claims description 7
- MIHQMPOIGDKUKL-UHFFFAOYSA-N ethyl 2-[[2-[benzoyl(cyclohexyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetate Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=CC=1C(C(=O)NCC(=O)OCC)N(C(=O)C=1C=CC=CC=1)C1CCCCC1 MIHQMPOIGDKUKL-UHFFFAOYSA-N 0.000 claims description 7
- 201000011066 hemangioma Diseases 0.000 claims description 7
- 201000001441 melanoma Diseases 0.000 claims description 7
- KUUGHSOSLOOGCL-UHFFFAOYSA-N methyl 3,5-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]benzoate Chemical compound C=1C(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)=CC(C(=O)OC)=CC=1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O KUUGHSOSLOOGCL-UHFFFAOYSA-N 0.000 claims description 7
- LGGVRGULJZCGPY-UHFFFAOYSA-N methyl 4-methyl-2,6-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]benzoate Chemical compound C1=C(C)C=C(OC=2C(=CC(=CC=2)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)C(C(=O)OC)=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O LGGVRGULJZCGPY-UHFFFAOYSA-N 0.000 claims description 7
- UFNXETVTJLOCQT-UHFFFAOYSA-N n,n-dimethyl-2,3-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propan-1-amine Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=C([N+]([O-])=O)C=1OC(CN(C)C)COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O UFNXETVTJLOCQT-UHFFFAOYSA-N 0.000 claims description 7
- NWUZHYPOPFDVLR-UHFFFAOYSA-N n-[2,3-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propyl]-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NCC(OC=1C(=CC(=CC=1)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O NWUZHYPOPFDVLR-UHFFFAOYSA-N 0.000 claims description 7
- UZAWRPDUFKYXLP-UHFFFAOYSA-N n-phenyl-5-(trifluoromethylsulfonylamino)-1h-indole-2-carboxamide Chemical compound C=1C2=CC(NS(=O)(=O)C(F)(F)F)=CC=C2NC=1C(=O)NC1=CC=CC=C1 UZAWRPDUFKYXLP-UHFFFAOYSA-N 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- BGXUGUACLSMSKQ-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[4-(trifluoromethylsulfonylamino)phenoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1OC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 BGXUGUACLSMSKQ-UHFFFAOYSA-N 0.000 claims description 6
- DBAWFAOOMJJQGY-UHFFFAOYSA-N 2-[3-[2-oxo-2-[3-(trifluoromethylsulfonyl)anilino]ethyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CC(=O)NC=2C=C(C=CC=2)S(=O)(=O)C(F)(F)F)=C1 DBAWFAOOMJJQGY-UHFFFAOYSA-N 0.000 claims description 6
- YIYHAQBOBXQPMY-UHFFFAOYSA-N 2-[4-[2-oxo-2-[3-(trifluoromethylsulfonyl)anilino]ethyl]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1CC(=O)NC1=CC=CC(S(=O)(=O)C(F)(F)F)=C1 YIYHAQBOBXQPMY-UHFFFAOYSA-N 0.000 claims description 6
- NVNJWHIEZHIRSK-UHFFFAOYSA-N 3-[[6-[[methyl(trifluoromethylsulfonyl)amino]methyl]naphthalene-2-carbonyl]amino]benzoic acid Chemical compound C1=CC2=CC(CN(C)S(=O)(=O)C(F)(F)F)=CC=C2C=C1C(=O)NC1=CC=CC(C(O)=O)=C1 NVNJWHIEZHIRSK-UHFFFAOYSA-N 0.000 claims description 6
- KTGOTASIUNVNNJ-UHFFFAOYSA-N 4-(trifluoromethylsulfonyl)-n-[[4-(trifluoromethylsulfonyl)phenyl]methyl]benzamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CNC(=O)C1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 KTGOTASIUNVNNJ-UHFFFAOYSA-N 0.000 claims description 6
- GPAJGRMLPDXROH-UHFFFAOYSA-N 6-(trifluoromethylsulfonylamino)naphthalene-2-carboxylic acid Chemical compound C1=C(NS(=O)(=O)C(F)(F)F)C=CC2=CC(C(=O)O)=CC=C21 GPAJGRMLPDXROH-UHFFFAOYSA-N 0.000 claims description 6
- 208000032612 Glial tumor Diseases 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 claims description 6
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 claims description 6
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- NQMMWURTYYXNFY-UHFFFAOYSA-N ethyl 2-[[2-[acetyl(cyclohexyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetate Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=CC=1C(C(=O)NCC(=O)OCC)N(C(C)=O)C1CCCCC1 NQMMWURTYYXNFY-UHFFFAOYSA-N 0.000 claims description 6
- DSEMYOGFGHISNO-UHFFFAOYSA-N ethyl 2-[[2-[acetyl(propyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetate Chemical compound CCOC(=O)CNC(=O)C(N(CCC)C(C)=O)C1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 DSEMYOGFGHISNO-UHFFFAOYSA-N 0.000 claims description 6
- 210000004185 liver Anatomy 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- MMNYEOQFOTXBLX-UHFFFAOYSA-N n-[4-(4-aminophenoxy)-4-phenoxycyclohexa-1,5-dien-1-yl]-1,1,1-trifluoromethanesulfonamide Chemical compound C1=CC(N)=CC=C1OC1(OC=2C=CC=CC=2)C=CC(NS(=O)(=O)C(F)(F)F)=CC1 MMNYEOQFOTXBLX-UHFFFAOYSA-N 0.000 claims description 6
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 claims description 6
- BZKUTKHDBUUNIC-UHFFFAOYSA-N 1-(trifluoromethylsulfonyl)-4-[[4-(trifluoromethylsulfonyl)phenyl]disulfanyl]benzene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1SSC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 BZKUTKHDBUUNIC-UHFFFAOYSA-N 0.000 claims description 5
- CHBRTXLDXSYCHQ-UHFFFAOYSA-N 4-[[[2-[2-methyl-5-(trifluoromethylsulfonylamino)indol-1-yl]acetyl]amino]methyl]benzoic acid Chemical compound CC1=CC2=CC(NS(=O)(=O)C(F)(F)F)=CC=C2N1CC(=O)NCC1=CC=C(C(O)=O)C=C1 CHBRTXLDXSYCHQ-UHFFFAOYSA-N 0.000 claims description 5
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 5
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 5
- 241000607734 Yersinia <bacteria> Species 0.000 claims description 5
- 210000001072 colon Anatomy 0.000 claims description 5
- 125000004494 ethyl ester group Chemical group 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 238000000099 in vitro assay Methods 0.000 claims description 5
- 210000004962 mammalian cell Anatomy 0.000 claims description 5
- GXMYOHOWHWDENR-UHFFFAOYSA-N methyl 2-[[2-[benzoyl(butyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetate Chemical compound C=1C=CC=CC=1C(=O)N(CCCC)C(C(=O)NCC(=O)OC)C1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 GXMYOHOWHWDENR-UHFFFAOYSA-N 0.000 claims description 5
- JXLIBXGEKVBOPO-UHFFFAOYSA-N n-[4-[3,6-di(propan-2-yl)-2-[4-(trifluoromethylsulfonylamino)phenyl]phenyl]phenyl]-1,1,1-trifluoromethanesulfonamide Chemical compound C=1C=C(NS(=O)(=O)C(F)(F)F)C=CC=1C=1C(C(C)C)=CC=C(C(C)C)C=1C1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 JXLIBXGEKVBOPO-UHFFFAOYSA-N 0.000 claims description 5
- 230000002611 ovarian Effects 0.000 claims description 5
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 claims description 5
- 125000004585 polycyclic heterocycle group Chemical group 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 4
- DCIRBOHLYMCVGC-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[2-[4-(trifluoromethylsulfonylamino)phenyl]ethyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1CCC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 DCIRBOHLYMCVGC-UHFFFAOYSA-N 0.000 claims description 4
- UDSXKRQWFHORJN-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[5-[4-(trifluoromethylsulfonylamino)phenyl]-1,3,4-oxadiazol-2-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1C1=NN=C(C=2C=CC(NS(=O)(=O)C(F)(F)F)=CC=2)O1 UDSXKRQWFHORJN-UHFFFAOYSA-N 0.000 claims description 4
- VOSZLOXPZFQVSI-UHFFFAOYSA-N 2-nitro-1-[[2-nitro-4-(trifluoromethylsulfonyl)phenyl]disulfanyl]-4-(trifluoromethylsulfonyl)benzene Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1SSC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O VOSZLOXPZFQVSI-UHFFFAOYSA-N 0.000 claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- 102000010995 Pleckstrin homology domains Human genes 0.000 claims description 4
- 108050001185 Pleckstrin homology domains Proteins 0.000 claims description 4
- 241000607479 Yersinia pestis Species 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 239000002773 nucleotide Substances 0.000 claims description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 4
- YBEPDTOTOCUWHF-REOHCLBHSA-N (2r)-2-(phosphonoamino)-3-sulfanylpropanoic acid Chemical compound OC(=O)[C@H](CS)NP(O)(O)=O YBEPDTOTOCUWHF-REOHCLBHSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- VSNMOPJTDBEUSP-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[3-[4-(trifluoromethylsulfonylamino)phenoxy]phenoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1OC1=CC=CC(OC=2C=CC(NS(=O)(=O)C(F)(F)F)=CC=2)=C1 VSNMOPJTDBEUSP-UHFFFAOYSA-N 0.000 claims description 3
- LWZSFGTYRUSKTN-UHFFFAOYSA-N 2-[4-(difluoromethylsulfonyl)phenyl]-5-naphthalen-2-yl-1,3-oxazole Chemical compound C1=CC(S(=O)(=O)C(F)F)=CC=C1C1=NC=C(C=2C=C3C=CC=CC3=CC=2)O1 LWZSFGTYRUSKTN-UHFFFAOYSA-N 0.000 claims description 3
- BLHBRJIMSVQCPL-UHFFFAOYSA-N 4-[[4-(morpholin-4-ylmethyl)-2,5-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]phenyl]methyl]morpholine Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1OC(C(=C1)CN2CCOCC2)=CC(CN2CCOCC2)=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1[N+]([O-])=O BLHBRJIMSVQCPL-UHFFFAOYSA-N 0.000 claims description 3
- 101710123299 Alkaline phosphatase L Proteins 0.000 claims description 3
- 102000004631 Calcineurin Human genes 0.000 claims description 3
- 108010042955 Calcineurin Proteins 0.000 claims description 3
- 102000006442 Class 2 Receptor-Like Protein Tyrosine Phosphatases Human genes 0.000 claims description 3
- 108010044260 Class 2 Receptor-Like Protein Tyrosine Phosphatases Proteins 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 102000002266 Dual-Specificity Phosphatases Human genes 0.000 claims description 3
- 108010000518 Dual-Specificity Phosphatases Proteins 0.000 claims description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 3
- 108010072039 Histidine kinase Proteins 0.000 claims description 3
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 102000005741 Metalloproteases Human genes 0.000 claims description 3
- 108010006035 Metalloproteases Proteins 0.000 claims description 3
- 108010032107 Non-Receptor Type 11 Protein Tyrosine Phosphatase Proteins 0.000 claims description 3
- 102000007607 Non-Receptor Type 11 Protein Tyrosine Phosphatase Human genes 0.000 claims description 3
- 108010015793 Non-Receptor Type 6 Protein Tyrosine Phosphatase Proteins 0.000 claims description 3
- 102000002001 Non-Receptor Type 6 Protein Tyrosine Phosphatase Human genes 0.000 claims description 3
- 108091034117 Oligonucleotide Proteins 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 101000752225 Xenopus laevis Low density lipoprotein receptor adapter protein 1-A Proteins 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 102000007588 cdc25 Phosphatases Human genes 0.000 claims description 3
- 108010046616 cdc25 Phosphatases Proteins 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 230000001926 lymphatic effect Effects 0.000 claims description 3
- 150000002678 macrocyclic compounds Chemical class 0.000 claims description 3
- 150000004702 methyl esters Chemical class 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 239000002777 nucleoside Substances 0.000 claims description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 3
- 229920002601 oligoester Polymers 0.000 claims description 3
- 229920001542 oligosaccharide Polymers 0.000 claims description 3
- 150000002482 oligosaccharides Chemical class 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical compound OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- OCAPWYYPSBCEQX-UHFFFAOYSA-N 1-(trifluoromethylsulfonyl)-4-[4-(trifluoromethylsulfonyl)phenoxy]benzene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 OCAPWYYPSBCEQX-UHFFFAOYSA-N 0.000 claims description 2
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 claims description 2
- JXIQQLOLRIIKIG-UHFFFAOYSA-N 3-[[5-(trifluoromethylsulfonylamino)-1h-indole-2-carbonyl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)C=2NC3=CC=C(NS(=O)(=O)C(F)(F)F)C=C3C=2)=C1 JXIQQLOLRIIKIG-UHFFFAOYSA-N 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 229950006137 dexfosfoserine Drugs 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 230000000926 neurological effect Effects 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 6
- LUVKDYPGCYLPTM-UHFFFAOYSA-N ethyl 2-[[2-[acetyl(methyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetate Chemical compound CCOC(=O)CNC(=O)C(N(C)C(C)=O)C1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 LUVKDYPGCYLPTM-UHFFFAOYSA-N 0.000 claims 4
- AIWBSAWVPKWHDL-UHFFFAOYSA-N tert-butyl 2-[2-methyl-5-(trifluoromethylsulfonylamino)indol-1-yl]acetate Chemical compound FC(F)(F)S(=O)(=O)NC1=CC=C2N(CC(=O)OC(C)(C)C)C(C)=CC2=C1 AIWBSAWVPKWHDL-UHFFFAOYSA-N 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- ZCBOAZHDJUWJKC-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[4-[4-(trifluoromethylsulfonylamino)phenoxy]butoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1OCCCCOC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 ZCBOAZHDJUWJKC-UHFFFAOYSA-N 0.000 claims 2
- ZGRRHTYFPRHUTL-UHFFFAOYSA-N 1-(4-nitroanilino)-3-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propan-2-ol Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=C([N+]([O-])=O)C=1OCC(O)CNC1=CC=C([N+]([O-])=O)C=C1 ZGRRHTYFPRHUTL-UHFFFAOYSA-N 0.000 claims 2
- ONWJVOBZCBGVBQ-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[4-[4-(trifluoromethylsulfonylamino)phenoxy]phenoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1OC(C=C1)=CC=C1OC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 ONWJVOBZCBGVBQ-UHFFFAOYSA-N 0.000 claims 1
- VLFLBRUQMBUMIQ-UHFFFAOYSA-N 1-(carboxymethyl)-5-(trifluoromethylsulfonylamino)indole-2-carboxylic acid Chemical compound FC(F)(F)S(=O)(=O)NC1=CC=C2N(CC(=O)O)C(C(O)=O)=CC2=C1 VLFLBRUQMBUMIQ-UHFFFAOYSA-N 0.000 claims 1
- ZYJNGRLTDBCOSY-UHFFFAOYSA-N 1-[2,3-bis[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]propyl]piperidine Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1OCC(OC=1C(=CC(=CC=1)S(=O)(=O)C(F)(F)F)[N+]([O-])=O)CN1CCCCC1 ZYJNGRLTDBCOSY-UHFFFAOYSA-N 0.000 claims 1
- PQHAPRCMMJPLRP-UHFFFAOYSA-N 2-[3-[2-oxo-2-[3-(trifluoromethylsulfonyl)anilino]ethyl]phenyl]-n-[3-(trifluoromethylsulfonyl)phenyl]acetamide Chemical compound FC(F)(F)S(=O)(=O)C1=CC=CC(NC(=O)CC=2C=C(CC(=O)NC=3C=C(C=CC=3)S(=O)(=O)C(F)(F)F)C=CC=2)=C1 PQHAPRCMMJPLRP-UHFFFAOYSA-N 0.000 claims 1
- AGXLDYSJDKHIQV-UHFFFAOYSA-N 2-[4-(difluoromethylsulfonyl)phenyl]-5-naphthalen-2-yl-1,3-oxazole N-(4-methylphenyl)-2-nitro-4-(1,1,2,2-tetrafluoroethylsulfonyl)aniline 1,1,1-trifluoro-N-[4-[2-[4-(trifluoromethylsulfonylamino)phenyl]ethyl]phenyl]methanesulfonamide Chemical compound FC(S(=O)(=O)NC1=CC=C(C=C1)CCC1=CC=C(C=C1)NS(=O)(=O)C(F)(F)F)(F)F.[N+](=O)([O-])C1=C(C=CC(=C1)S(=O)(=O)C(C(F)F)(F)F)NC1=CC=C(C=C1)C.FC(S(=O)(=O)C1=CC=C(C=C1)C=1OC(=CN1)C1=CC2=CC=CC=C2C=C1)F AGXLDYSJDKHIQV-UHFFFAOYSA-N 0.000 claims 1
- VMYDJAVYPAAGOP-UHFFFAOYSA-N 2-[4-[2-oxo-2-[4-(trifluoromethylsulfonyl)anilino]ethyl]phenyl]-n-[4-(trifluoromethylsulfonyl)phenyl]acetamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1NC(=O)CC(C=C1)=CC=C1CC(=O)NC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 VMYDJAVYPAAGOP-UHFFFAOYSA-N 0.000 claims 1
- 208000009956 adenocarcinoma Diseases 0.000 claims 1
- POCFBDFTJMJWLG-UHFFFAOYSA-N dihydrosinapic acid methyl ester Natural products COC(=O)CCC1=CC(OC)=C(O)C(OC)=C1 POCFBDFTJMJWLG-UHFFFAOYSA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- SKACKRLYUNTQOR-UHFFFAOYSA-N ethyl 3-[[4-[1-ethyl-5-(trifluoromethylsulfonyl)benzimidazol-2-yl]benzoyl]amino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC(=O)C=2C=CC(=CC=2)C=2N(C3=CC=C(C=C3N=2)S(=O)(=O)C(F)(F)F)CC)=C1 SKACKRLYUNTQOR-UHFFFAOYSA-N 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- IBDIPERALKKVMK-UHFFFAOYSA-N n-(4-methylphenyl)-2-nitro-4-(1,1,2,2-tetrafluoroethylsulfonyl)aniline Chemical compound C1=CC(C)=CC=C1NC1=CC=C(S(=O)(=O)C(F)(F)C(F)F)C=C1[N+]([O-])=O IBDIPERALKKVMK-UHFFFAOYSA-N 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000002381 testicular Effects 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 143
- 239000000203 mixture Substances 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 49
- 235000019439 ethyl acetate Nutrition 0.000 description 49
- 239000007787 solid Substances 0.000 description 41
- 229940088598 enzyme Drugs 0.000 description 40
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 229910001868 water Inorganic materials 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 239000012267 brine Substances 0.000 description 27
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 27
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- 229960000583 acetic acid Drugs 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 102000005962 receptors Human genes 0.000 description 22
- 108020003175 receptors Proteins 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 229910000104 sodium hydride Inorganic materials 0.000 description 18
- 230000002401 inhibitory effect Effects 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 239000000758 substrate Substances 0.000 description 14
- 102000004877 Insulin Human genes 0.000 description 13
- 108090001061 Insulin Proteins 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 229940125396 insulin Drugs 0.000 description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 12
- 230000011664 signaling Effects 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 230000030609 dephosphorylation Effects 0.000 description 11
- 238000006209 dephosphorylation reaction Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 230000003647 oxidation Effects 0.000 description 11
- 238000007254 oxidation reaction Methods 0.000 description 11
- 230000026731 phosphorylation Effects 0.000 description 11
- 238000006366 phosphorylation reaction Methods 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 11
- BDIMBZRJVHLTPD-UHFFFAOYSA-N 1-chloro-2-nitro-4-(trifluoromethylsulfonyl)benzene Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1Cl BDIMBZRJVHLTPD-UHFFFAOYSA-N 0.000 description 10
- OPAXHVNZGUGCKW-UHFFFAOYSA-N 4-(trifluoromethylsulfanyl)benzaldehyde Chemical compound FC(F)(F)SC1=CC=C(C=O)C=C1 OPAXHVNZGUGCKW-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 125000005647 linker group Chemical group 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 239000000969 carrier Substances 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 230000001086 cytosolic effect Effects 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 102000003746 Insulin Receptor Human genes 0.000 description 8
- 108010001127 Insulin Receptor Proteins 0.000 description 8
- 102100028516 Receptor-type tyrosine-protein phosphatase U Human genes 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 108010010803 Gelatin Proteins 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000006184 cosolvent Substances 0.000 description 7
- 239000008273 gelatin Substances 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 230000003278 mimic effect Effects 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- 125000005152 trihalomethanesulfonyl group Chemical group 0.000 description 7
- 101000878540 Homo sapiens Protein-tyrosine kinase 2-beta Proteins 0.000 description 6
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 6
- 229910052770 Uranium Inorganic materials 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 230000024245 cell differentiation Effects 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 125000005499 phosphonyl group Chemical group 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 125000005309 thioalkoxy group Chemical group 0.000 description 6
- 125000005296 thioaryloxy group Chemical group 0.000 description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 6
- 125000005404 thioheteroaryloxy group Chemical group 0.000 description 6
- 125000005190 thiohydroxy group Chemical group 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 125000005423 trihalomethanesulfonamido group Chemical group 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- 101150026303 HEX1 gene Proteins 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 108060006633 protein kinase Proteins 0.000 description 5
- 150000003457 sulfones Chemical class 0.000 description 5
- QTJXVIKNLHZIKL-UHFFFAOYSA-N sulfur difluoride Chemical class FSF QTJXVIKNLHZIKL-UHFFFAOYSA-N 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- PVPZMAOFUOXVHI-UHFFFAOYSA-N 1-chloro-4-(trifluoromethylsulfonyl)benzene Chemical compound FC(F)(F)S(=O)(=O)C1=CC=C(Cl)C=C1 PVPZMAOFUOXVHI-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 208000035473 Communicable disease Diseases 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- 208000029462 Immunodeficiency disease Diseases 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 4
- 108091008606 PDGF receptors Proteins 0.000 description 4
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 101150056500 Ptpn6 gene Proteins 0.000 description 4
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 description 4
- 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000007664 blowing Methods 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000033077 cellular process Effects 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 230000007813 immunodeficiency Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- RNVFYQUEEMZKLR-UHFFFAOYSA-N methyl 3,5-dihydroxybenzoate Chemical compound COC(=O)C1=CC(O)=CC(O)=C1 RNVFYQUEEMZKLR-UHFFFAOYSA-N 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000002018 overexpression Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- LSJNBGSOIVSBBR-UHFFFAOYSA-N thionyl fluoride Chemical class FS(F)=O LSJNBGSOIVSBBR-UHFFFAOYSA-N 0.000 description 4
- 229940086542 triethylamine Drugs 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010061598 Immunodeficiency Diseases 0.000 description 3
- 108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 3
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 208000007502 anemia Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 3
- 108020001778 catalytic domains Proteins 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000000302 molecular modelling Methods 0.000 description 3
- WCJAUCQIJASRBF-UHFFFAOYSA-N n-[[4-(trifluoromethylsulfanyl)phenyl]methyl]benzamide Chemical compound C1=CC(SC(F)(F)F)=CC=C1CNC(=O)C1=CC=CC=C1 WCJAUCQIJASRBF-UHFFFAOYSA-N 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000012264 purified product Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 102000009076 src-Family Kinases Human genes 0.000 description 3
- 108010087686 src-Family Kinases Proteins 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- LBCBCGIYICAOFP-UHFFFAOYSA-N 1,1,1-trifluoro-n-[4-[3-[4-(trifluoromethylsulfonylamino)phenoxy]propoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1OCCCOC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 LBCBCGIYICAOFP-UHFFFAOYSA-N 0.000 description 2
- XJWOEGMPXJAQLA-UHFFFAOYSA-N 1-(trifluoromethylsulfanyl)-4-[[4-(trifluoromethylsulfanyl)phenyl]methoxymethyl]benzene Chemical compound C1=CC(SC(F)(F)F)=CC=C1COCC1=CC=C(SC(F)(F)F)C=C1 XJWOEGMPXJAQLA-UHFFFAOYSA-N 0.000 description 2
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- MMEDJBFVJUFIDD-UHFFFAOYSA-N 2-[2-(carboxymethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1CC(O)=O MMEDJBFVJUFIDD-UHFFFAOYSA-N 0.000 description 2
- GDYYIJNDPMFMTB-UHFFFAOYSA-N 2-[3-(carboxymethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CC(O)=O)=C1 GDYYIJNDPMFMTB-UHFFFAOYSA-N 0.000 description 2
- LZYNHEOVZMLXIO-UHFFFAOYSA-N 3-(trifluoromethylsulfonyl)aniline Chemical compound NC1=CC=CC(S(=O)(=O)C(F)(F)F)=C1 LZYNHEOVZMLXIO-UHFFFAOYSA-N 0.000 description 2
- DEDKCEDXZJIDKZ-UHFFFAOYSA-N 4-(3-hydroxyphenoxy)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=CC(O)=C1 DEDKCEDXZJIDKZ-UHFFFAOYSA-N 0.000 description 2
- JCRRFJIVUPSNTA-UHFFFAOYSA-N 4-[4-(4-aminophenoxy)phenoxy]aniline Chemical compound C1=CC(N)=CC=C1OC(C=C1)=CC=C1OC1=CC=C(N)C=C1 JCRRFJIVUPSNTA-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 108010044214 Class 3 Receptor-Like Protein Tyrosine Phosphatases Proteins 0.000 description 2
- 102000006453 Class 3 Receptor-Like Protein Tyrosine Phosphatases Human genes 0.000 description 2
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 2
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 101000617289 Homo sapiens Tyrosine-protein phosphatase non-receptor type 9 Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 239000007836 KH2PO4 Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 2
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 206010062237 Renal impairment Diseases 0.000 description 2
- 102000014400 SH2 domains Human genes 0.000 description 2
- 108050003452 SH2 domains Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102100021722 Tyrosine-protein phosphatase non-receptor type 9 Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- LACURGWEZCFLBO-UHFFFAOYSA-N [4-(trifluoromethylsulfanyl)phenyl]methanamine Chemical compound NCC1=CC=C(SC(F)(F)F)C=C1 LACURGWEZCFLBO-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000005983 bone marrow dysfunction Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000012866 crystallographic experiment Methods 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- UQOUOXLHXPHDHF-UHFFFAOYSA-N diethyl 2,5-dihydroxybenzene-1,4-dicarboxylate Chemical compound CCOC(=O)C1=CC(O)=C(C(=O)OCC)C=C1O UQOUOXLHXPHDHF-UHFFFAOYSA-N 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 2
- YTHKOHNRPCSASL-UHFFFAOYSA-N ethyl 2-[4-(4-hydroxyphenyl)sulfonylphenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1S(=O)(=O)C1=CC=C(O)C=C1 YTHKOHNRPCSASL-UHFFFAOYSA-N 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- CUOFPKMEMCJTFX-UHFFFAOYSA-N ethyl 3-ethyl-5-nitro-1h-indole-2-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2C(CC)=C(C(=O)OCC)NC2=C1 CUOFPKMEMCJTFX-UHFFFAOYSA-N 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 210000004524 haematopoietic cell Anatomy 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 230000005977 kidney dysfunction Effects 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000005976 liver dysfunction Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- HHQJWDKIRXRTLS-UHFFFAOYSA-N n'-bromobutanediamide Chemical compound NC(=O)CCC(=O)NBr HHQJWDKIRXRTLS-UHFFFAOYSA-N 0.000 description 2
- QWZAZICSCBBSON-UHFFFAOYSA-N n,n-bis[[4-(trifluoromethylsulfanyl)phenyl]methyl]benzamide Chemical compound C1=CC(SC(F)(F)F)=CC=C1CN(C(=O)C=1C=CC=CC=1)CC1=CC=C(SC(F)(F)F)C=C1 QWZAZICSCBBSON-UHFFFAOYSA-N 0.000 description 2
- FSBLVBBRXSCOKU-UHFFFAOYSA-N n-butyl isocyanide Chemical compound CCCC[N+]#[C-] FSBLVBBRXSCOKU-UHFFFAOYSA-N 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 238000006384 oligomerization reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 102220316998 rs780388475 Human genes 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 125000004385 trihaloalkyl group Chemical group 0.000 description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical class [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 2
- 230000004862 vasculogenesis Effects 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- ONHKSMMMQXGGGQ-MSQVLRTGSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol;phosphoric acid Chemical class OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ONHKSMMMQXGGGQ-MSQVLRTGSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- HGDXFLPNVJYUFS-KNIFDHDWSA-N (2s)-2-amino-3-phosphonooxypropanoic acid;(2s)-3-(1h-imidazol-5-yl)-2-(phosphonoamino)propanoic acid Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O.OP(=O)(O)N[C@H](C(=O)O)CC1=CNC=N1 HGDXFLPNVJYUFS-KNIFDHDWSA-N 0.000 description 1
- NJYFRQQXXXRJHK-UHFFFAOYSA-N (4-aminophenyl) thiocyanate Chemical compound NC1=CC=C(SC#N)C=C1 NJYFRQQXXXRJHK-UHFFFAOYSA-N 0.000 description 1
- BLPOUZDLIYAHLN-UHFFFAOYSA-N (4-formyl-5-hydroxy-6-methylpyridin-3-yl)methyl phosphono hydrogen phosphate Chemical compound CC1=NC=C(COP(O)(=O)OP(O)(O)=O)C(C=O)=C1O BLPOUZDLIYAHLN-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- GXMWAEUSLYBHDR-UHFFFAOYSA-N 1,1,1-trifluoro-n-[3-methyl-4-[2-[2-methyl-4-(trifluoromethylsulfonylamino)phenyl]ethyl]phenyl]methanesulfonamide Chemical compound CC1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1CCC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1C GXMWAEUSLYBHDR-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- VAYGJBCOCRVROJ-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethylsulfanyl)benzene Chemical compound FC(F)(F)SC1=CC=C(CBr)C=C1 VAYGJBCOCRVROJ-UHFFFAOYSA-N 0.000 description 1
- HOCAZXWFYDLMQM-UHFFFAOYSA-N 1-(trifluoromethylsulfanyl)-4-[[4-(trifluoromethylsulfonyl)phenoxy]methyl]benzene Chemical compound C1=CC(SC(F)(F)F)=CC=C1COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 HOCAZXWFYDLMQM-UHFFFAOYSA-N 0.000 description 1
- XPVUQBZKPGEGTD-UHFFFAOYSA-N 1-(trifluoromethylsulfonyl)-4-[2-[4-(trifluoromethylsulfonyl)phenyl]ethyl]benzene Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CCC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 XPVUQBZKPGEGTD-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- CQQBVMXLTBXNLB-UHFFFAOYSA-N 1-bromo-4-(trifluoromethylsulfanyl)benzene Chemical compound FC(F)(F)SC1=CC=C(Br)C=C1 CQQBVMXLTBXNLB-UHFFFAOYSA-N 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- DGGCIZWVIVXHFR-UHFFFAOYSA-N 2,5-bis(morpholin-4-ylmethyl)benzene-1,4-diol Chemical compound OC=1C=C(CN2CCOCC2)C(O)=CC=1CN1CCOCC1 DGGCIZWVIVXHFR-UHFFFAOYSA-N 0.000 description 1
- HGGWOSYNRVOQJH-UHFFFAOYSA-N 2-(4-methylsulfonylphenyl)acetic acid Chemical compound CS(=O)(=O)C1=CC=C(CC(O)=O)C=C1 HGGWOSYNRVOQJH-UHFFFAOYSA-N 0.000 description 1
- JQSKYLMRBFOYTR-UHFFFAOYSA-N 2-(trifluoromethylsulfanyl)benzaldehyde Chemical compound FC(F)(F)SC1=CC=CC=C1C=O JQSKYLMRBFOYTR-UHFFFAOYSA-N 0.000 description 1
- SLWIPPZWFZGHEU-UHFFFAOYSA-N 2-[4-(carboxymethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(CC(O)=O)C=C1 SLWIPPZWFZGHEU-UHFFFAOYSA-N 0.000 description 1
- SCNMARBIKQIGBI-UHFFFAOYSA-N 2-[4-[2-oxo-2-[3-(trifluoromethylsulfonyl)anilino]ethyl]phenyl]-n-[3-(trifluoromethylsulfonyl)phenyl]acetamide Chemical compound FC(F)(F)S(=O)(=O)C1=CC=CC(NC(=O)CC=2C=CC(CC(=O)NC=3C=C(C=CC=3)S(=O)(=O)C(F)(F)F)=CC=2)=C1 SCNMARBIKQIGBI-UHFFFAOYSA-N 0.000 description 1
- CSTAKRHRYRCVAB-UHFFFAOYSA-N 2-[[2-[acetyl(methyl)amino]-2-[4-(trifluoromethylsulfonyl)phenyl]acetyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)C(N(C)C(C)=O)C1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 CSTAKRHRYRCVAB-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- DNJLFZHMJDSJFN-UHFFFAOYSA-N 2-isocyano-1,3-dimethylbenzene Chemical compound CC1=CC=CC(C)=C1[N+]#[C-] DNJLFZHMJDSJFN-UHFFFAOYSA-N 0.000 description 1
- IDJGRXQMAHESOD-UHFFFAOYSA-N 2-methyl-5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC(C)=CC2=C1 IDJGRXQMAHESOD-UHFFFAOYSA-N 0.000 description 1
- DHCJQRNKEXCLCE-UHFFFAOYSA-N 2-phenoxy-2-phenylpropanoic acid Chemical class C=1C=CC=CC=1C(C)(C(O)=O)OC1=CC=CC=C1 DHCJQRNKEXCLCE-UHFFFAOYSA-N 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- DJSPXQHYPNNHEM-UHFFFAOYSA-N 2-sulfonyl-1h-1,3,5-triazine Chemical class O=S(=O)=C1N=CN=CN1 DJSPXQHYPNNHEM-UHFFFAOYSA-N 0.000 description 1
- VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 1
- QCMHUGYTOGXZIW-UHFFFAOYSA-N 3-(dimethylamino)propane-1,2-diol Chemical compound CN(C)CC(O)CO QCMHUGYTOGXZIW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- VZBNUEHCOOXOHR-UHFFFAOYSA-N 3-morpholin-4-ylpropane-1,2-diol Chemical compound OCC(O)CN1CCOCC1 VZBNUEHCOOXOHR-UHFFFAOYSA-N 0.000 description 1
- WILRYNZYUBOMJX-UHFFFAOYSA-N 3-piperazin-1-yl-1,2-benzothiazepine Chemical class C1CNCCN1C1=NSC2=CC=CC=C2C=C1 WILRYNZYUBOMJX-UHFFFAOYSA-N 0.000 description 1
- UTRXBXRDWKORHB-UHFFFAOYSA-N 4-(2,3-dihydroxypropylamino)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(NCC(O)CO)C=C1 UTRXBXRDWKORHB-UHFFFAOYSA-N 0.000 description 1
- YSOHISZFXGJBBY-UHFFFAOYSA-N 4-(trifluoromethyl)-n-[[4-(trifluoromethylsulfanyl)phenyl]methyl]benzenecarbothioamide Chemical compound C1=CC(SC(F)(F)F)=CC=C1CNC(=S)C1=CC=C(C(F)(F)F)C=C1 YSOHISZFXGJBBY-UHFFFAOYSA-N 0.000 description 1
- UMOGQQWVQUQTQA-UHFFFAOYSA-N 4-(trifluoromethylsulfanyl)benzoic acid Chemical compound OC(=O)C1=CC=C(SC(F)(F)F)C=C1 UMOGQQWVQUQTQA-UHFFFAOYSA-N 0.000 description 1
- HLBLWEWZXPIGSM-UHFFFAOYSA-N 4-Aminophenyl ether Chemical compound C1=CC(N)=CC=C1OC1=CC=C(N)C=C1 HLBLWEWZXPIGSM-UHFFFAOYSA-N 0.000 description 1
- ISESBQNCWCFFFR-UHFFFAOYSA-N 4-[2-(4-amino-2-methylphenyl)ethyl]-3-methylaniline Chemical group CC1=CC(N)=CC=C1CCC1=CC=C(N)C=C1C ISESBQNCWCFFFR-UHFFFAOYSA-N 0.000 description 1
- RYYUUQPLFHRZOY-UHFFFAOYSA-N 4-[2-(4-aminophenoxy)phenoxy]aniline Chemical compound C1=CC(N)=CC=C1OC1=CC=CC=C1OC1=CC=C(N)C=C1 RYYUUQPLFHRZOY-UHFFFAOYSA-N 0.000 description 1
- HPUJEBAZZTZOFL-UHFFFAOYSA-N 4-[3-(4-aminophenoxy)-2,2-dimethylpropoxy]aniline Chemical compound C=1C=C(N)C=CC=1OCC(C)(C)COC1=CC=C(N)C=C1 HPUJEBAZZTZOFL-UHFFFAOYSA-N 0.000 description 1
- LAFZPVANKKJENB-UHFFFAOYSA-N 4-[4-(4-aminophenoxy)butoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCCCOC1=CC=C(N)C=C1 LAFZPVANKKJENB-UHFFFAOYSA-N 0.000 description 1
- MJZXFMSIHMJQBW-UHFFFAOYSA-N 4-[5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NN=C(C=2C=CC(N)=CC=2)O1 MJZXFMSIHMJQBW-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- NKFIBMOQAPEKNZ-UHFFFAOYSA-N 5-amino-1h-indole-2-carboxylic acid Chemical compound NC1=CC=C2NC(C(O)=O)=CC2=C1 NKFIBMOQAPEKNZ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Chemical class O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- UJOBWOGCFQCDNV-UHFFFAOYSA-N Carbazole Natural products C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 1
- 102000003846 Carbonic anhydrases Human genes 0.000 description 1
- 108090000209 Carbonic anhydrases Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 241001137307 Cyprinodon variegatus Species 0.000 description 1
- GSXOAOHZAIYLCY-UHFFFAOYSA-N D-F6P Natural products OCC(=O)C(O)C(O)C(O)COP(O)(O)=O GSXOAOHZAIYLCY-UHFFFAOYSA-N 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- 108010023873 DADEpYL-NH2 Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010011953 Decreased activity Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- PSCXEUSWZWRCMQ-UHFFFAOYSA-N F[S](F)F Chemical class F[S](F)F PSCXEUSWZWRCMQ-UHFFFAOYSA-N 0.000 description 1
- VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 102000002090 Fibronectin type III Human genes 0.000 description 1
- 108050009401 Fibronectin type III Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- GVVPGTZRZFNKDS-YFHOEESVSA-N Geranyl diphosphate Natural products CC(C)=CCC\C(C)=C/COP(O)(=O)OP(O)(O)=O GVVPGTZRZFNKDS-YFHOEESVSA-N 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 description 1
- 101000606506 Homo sapiens Receptor-type tyrosine-protein phosphatase eta Proteins 0.000 description 1
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 description 1
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 1
- 101001087416 Homo sapiens Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 1
- 108010024121 Janus Kinases Proteins 0.000 description 1
- 102000015617 Janus Kinases Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- IFKCGICFCPUXLZ-UHFFFAOYSA-N N,N-diethylethanamine hexane Chemical compound CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCN(CC)CC IFKCGICFCPUXLZ-UHFFFAOYSA-N 0.000 description 1
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-L O(4)-phosphonato-L-tyrosine(2-) Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1=CC=C(OP([O-])([O-])=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-L 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102100039808 Receptor-type tyrosine-protein phosphatase eta Human genes 0.000 description 1
- 101150036867 SYP gene Proteins 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 102000004584 Somatomedin Receptors Human genes 0.000 description 1
- 108010017622 Somatomedin Receptors Proteins 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 240000006474 Theobroma bicolor Species 0.000 description 1
- 102000000887 Transcription factor STAT Human genes 0.000 description 1
- 108050007918 Transcription factor STAT Proteins 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 241000287433 Turdus Species 0.000 description 1
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 1
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 1
- 238000006058 Ugi-reaction Methods 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- KCWQNXIWNNTUIJ-UHFFFAOYSA-N [4-(trifluoromethylsulfanyl)phenyl]methanol Chemical compound OCC1=CC=C(SC(F)(F)F)C=C1 KCWQNXIWNNTUIJ-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- UUTVVALNQPWIEX-UHFFFAOYSA-N [bromo(trifluoromethylsulfanyl)methyl]benzene Chemical compound FC(F)(F)SC(Br)C1=CC=CC=C1 UUTVVALNQPWIEX-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- BGWGXPAPYGQALX-ARQDHWQXSA-N beta-D-fructofuranose 6-phosphate Chemical compound OC[C@@]1(O)O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O BGWGXPAPYGQALX-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Chemical class O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Chemical class O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 230000008416 bone turnover Effects 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 201000006824 bubonic plague Diseases 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000033026 cell fate determination Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 239000003224 coccidiostatic agent Substances 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- YNAAFGQNGMFIHH-UHFFFAOYSA-N ctk8g8788 Chemical class [S]F YNAAFGQNGMFIHH-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical class 0.000 description 1
- CHVJITGCYZJHLR-UHFFFAOYSA-N cyclohepta-1,3,5-triene Chemical compound C1C=CC=CC=C1 CHVJITGCYZJHLR-UHFFFAOYSA-N 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- DBKKFIIYQGGHJO-UHFFFAOYSA-N diethyl 2-oxopropanedioate Chemical compound CCOC(=O)C(=O)C(=O)OCC DBKKFIIYQGGHJO-UHFFFAOYSA-N 0.000 description 1
- QSACPWSIIRFHHR-UHFFFAOYSA-N dimethylphenyl isocyanide Natural products CC1=CC=CC(C)=C1C#N QSACPWSIIRFHHR-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008846 dynamic interplay Effects 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- DTGUXIWYZIAUIT-UHFFFAOYSA-N ethyl 1-methyl-5-nitroindole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2N(C)C(C(=O)OCC)=CC2=C1 DTGUXIWYZIAUIT-UHFFFAOYSA-N 0.000 description 1
- YWBSNNWDEDWAKZ-UHFFFAOYSA-N ethyl 3-amino-2-ethylbenzoate Chemical compound CCOC(=O)C1=CC=CC(N)=C1CC YWBSNNWDEDWAKZ-UHFFFAOYSA-N 0.000 description 1
- WPRKJQVJYKGTLF-UHFFFAOYSA-N ethyl 5-amino-1-methylindole-2-carboxylate Chemical compound NC1=CC=C2N(C)C(C(=O)OCC)=CC2=C1 WPRKJQVJYKGTLF-UHFFFAOYSA-N 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 230000008622 extracellular signaling Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- GVVPGTZRZFNKDS-JXMROGBWSA-N geranyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O GVVPGTZRZFNKDS-JXMROGBWSA-N 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000000020 growth cone Anatomy 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 230000004155 insulin signaling pathway Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- IPFXNYPSBSIFOB-UHFFFAOYSA-N isopentyl pyrophosphate Chemical compound CC(C)CCO[P@](O)(=O)OP(O)(O)=O IPFXNYPSBSIFOB-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- LMLSBPHXMGSGCR-UHFFFAOYSA-N methyl 2-(3,5-dihydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC(O)=CC(O)=C1 LMLSBPHXMGSGCR-UHFFFAOYSA-N 0.000 description 1
- CRXFROMHHBMNAB-UHFFFAOYSA-N methyl 2-isocyanoacetate Chemical compound COC(=O)C[N+]#[C-] CRXFROMHHBMNAB-UHFFFAOYSA-N 0.000 description 1
- FEIOASZZURHTHB-UHFFFAOYSA-N methyl 4-formylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000012900 molecular simulation Methods 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- WCQUINJZYNOWRE-UHFFFAOYSA-N n,n-bis[[4-(trifluoromethylsulfonyl)phenyl]methyl]benzamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CN(C(=O)C=1C=CC=CC=1)CC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 WCQUINJZYNOWRE-UHFFFAOYSA-N 0.000 description 1
- XGZVNVFLUGNOJQ-UHFFFAOYSA-N n,n-dimethylformamide;ethyl acetate Chemical compound CN(C)C=O.CCOC(C)=O XGZVNVFLUGNOJQ-UHFFFAOYSA-N 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- SEVSMVUOKAMPDO-UHFFFAOYSA-N para-Acetoxybenzaldehyde Natural products CC(=O)OC1=CC=C(C=O)C=C1 SEVSMVUOKAMPDO-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- FCSJSCWHSZYMKN-UHFFFAOYSA-N pentyl 1H-benzimidazole-2-carboxylate Chemical compound C(CCCC)OC(=O)C=1NC2=C(N=1)C=CC=C2 FCSJSCWHSZYMKN-UHFFFAOYSA-N 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- BFVXHNQEHHHODD-UHFFFAOYSA-N phenyl-[2-(trifluoromethylsulfonyl)phenyl]methanone Chemical compound FC(F)(F)S(=O)(=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 BFVXHNQEHHHODD-UHFFFAOYSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- FDIKHVQUPVCJFA-UHFFFAOYSA-N phosphohistidine Chemical compound OP(=O)(O)NC(C(=O)O)CC1=CN=CN1 FDIKHVQUPVCJFA-UHFFFAOYSA-N 0.000 description 1
- 239000003358 phospholipase A2 inhibitor Substances 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011363 regulation of cellular process Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- OUGXVMIOSSJAFK-UHFFFAOYSA-M sodium;dichloromethane;hydrogen carbonate Chemical compound [Na+].ClCCl.OC([O-])=O OUGXVMIOSSJAFK-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000010421 standard material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- BFMKBYZEJOQYIM-UCGGBYDDSA-N tert-butyl (2s,4s)-4-diphenylphosphanyl-2-(diphenylphosphanylmethyl)pyrrolidine-1-carboxylate Chemical compound C([C@@H]1C[C@@H](CN1C(=O)OC(C)(C)C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 BFMKBYZEJOQYIM-UCGGBYDDSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 229960002363 thiamine pyrophosphate Drugs 0.000 description 1
- 235000008170 thiamine pyrophosphate Nutrition 0.000 description 1
- 239000011678 thiamine pyrophosphate Substances 0.000 description 1
- YXVCLPJQTZXJLH-UHFFFAOYSA-N thiamine(1+) diphosphate chloride Chemical compound [Cl-].CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N YXVCLPJQTZXJLH-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- CAUONNQGFXOEMY-UHFFFAOYSA-N tributyl(2-tributylstannylethynyl)stannane Chemical group CCCC[Sn](CCCC)(CCCC)C#C[Sn](CCCC)(CCCC)CCCC CAUONNQGFXOEMY-UHFFFAOYSA-N 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- UPGBQYFXKAKWQC-UHFFFAOYSA-N trifluoromethylsulfonylbenzene Chemical compound FC(F)(F)S(=O)(=O)C1=CC=CC=C1 UPGBQYFXKAKWQC-UHFFFAOYSA-N 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Chemical class OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 150000003681 vanadium Chemical class 0.000 description 1
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/09—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton the carbon skeleton being further substituted by at least two halogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/14—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
- C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
- C07C317/40—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/48—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C317/50—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
- C07C323/65—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfone or sulfoxide groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
- C07D231/24—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms having sulfone or sulfonic acid radicals in the molecule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15097099P | 1999-08-27 | 1999-08-27 | |
US16536599P | 1999-11-12 | 1999-11-12 | |
PCT/US2000/023293 WO2001016097A1 (fr) | 1999-08-27 | 2000-08-25 | Mimetiques phosphates et procedes de traitement utilisant des inhibiteurs de phosphatase |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ517426A true NZ517426A (en) | 2004-04-30 |
Family
ID=26848202
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ517426A NZ517426A (en) | 1999-08-27 | 2000-08-25 | Phosphate mimics and methods of treatment using phosphatase inhibitors |
Country Status (12)
Country | Link |
---|---|
US (2) | US6596772B1 (fr) |
EP (1) | EP1212296B9 (fr) |
JP (1) | JP2003508382A (fr) |
AT (1) | ATE309207T1 (fr) |
AU (1) | AU775625B2 (fr) |
CA (1) | CA2382789A1 (fr) |
DE (1) | DE60023920T2 (fr) |
ES (1) | ES2252058T3 (fr) |
IL (1) | IL148243A0 (fr) |
NZ (1) | NZ517426A (fr) |
WO (1) | WO2001016097A1 (fr) |
ZA (1) | ZA200201609B (fr) |
Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60045474D1 (de) | 1999-01-13 | 2011-02-17 | Univ New York State Res Found | Neues verfahren zum erschaffen von proteinkinase-inhibitoren |
TWI262185B (en) * | 1999-10-01 | 2006-09-21 | Eisai Co Ltd | Carboxylic acid derivatives having anti-hyperglycemia and anti-hyperlipemia action, and pharmaceutical composition containing the derivatives |
US20090124690A1 (en) * | 2000-04-03 | 2009-05-14 | Alberte Randall S | Generation of Combinatorial Synthetic Libraries and Screening for Novel Proadhesins and Nonadhesins |
SE0102299D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
EP1438044A1 (fr) | 2001-10-19 | 2004-07-21 | Transtech Pharma, Inc. | Bis-heteroaryl alcanes utilises comme agents therapeutiques |
US7005445B2 (en) | 2001-10-22 | 2006-02-28 | The Research Foundation Of State University Of New York | Protein kinase and phosphatase inhibitors and methods for designing them |
CA2464214C (fr) * | 2001-10-22 | 2011-02-08 | The Research Foundation Of State University Of New York | Inhibiteurs de proteines kinases et de proteines phosphatases, methodes d'identification et methodes d'utilisation associees |
EP1446487A1 (fr) * | 2001-11-13 | 2004-08-18 | Sugen, Inc. | Phosphatases proteiques de mammiferes |
US20040014699A1 (en) * | 2002-07-18 | 2004-01-22 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTPRM expression |
CN1708477A (zh) * | 2002-10-30 | 2005-12-14 | 日本曹达株式会社 | 使用二苯砜衍生物的记录材料及新颖的二苯砜衍生物化合物 |
DE10256182A1 (de) * | 2002-12-02 | 2004-06-24 | Merck Patent Gmbh | 2-Oxadiazolchromonderivate |
US20040186151A1 (en) * | 2003-02-12 | 2004-09-23 | Mjalli Adnan M.M. | Substituted azole derivatives as therapeutic agents |
EP1594847A2 (fr) * | 2003-02-12 | 2005-11-16 | Transtech Pharma, Inc. | Utilisation de derives d'azoles substitues en tant qu'agents therapeutiques |
US20050154011A1 (en) * | 2003-02-20 | 2005-07-14 | The Procter & Gamble Company | Tetrahydroisoquinolnyl sulfamic acids |
US7141596B2 (en) | 2003-10-08 | 2006-11-28 | Incyte Corporation | Inhibitors of proteins that bind phosphorylated molecules |
AU2003297904A1 (en) * | 2003-12-12 | 2005-07-14 | University Of Maryland, Baltimore | Immunomodulatory compounds that target and inhibit the py+3 binding site of tyrosene kinase p56 lck sh2 domain |
EP1730118A1 (fr) * | 2004-02-12 | 2006-12-13 | Transtech Pharma, Inc. | Derives d'azole substitues, compositions, et procedes d'utilisation |
EP1765332A2 (fr) * | 2004-06-17 | 2007-03-28 | Cengent Therapeutics, Inc. | Modulateurs a base d'azote trisubstitue de tyrosine phosphatases |
JP2008505916A (ja) * | 2004-07-09 | 2008-02-28 | メタバシス・セラピューティクス・インコーポレイテッド | チロシンホスファターゼの酸素/窒素複素環阻害剤 |
WO2006028970A1 (fr) * | 2004-09-02 | 2006-03-16 | Cengent Therapeutics, Inc. | Derives d'inhibiteurs de thiazole et de thiadiazole de tyrosine phosphatases |
BRPI0517925A (pt) | 2004-11-02 | 2008-10-21 | Pfizer | derivados de sulfonil benzimidazol |
DE102005055354A1 (de) * | 2005-11-21 | 2007-10-31 | Merck Patent Gmbh | Substituierte 5-Phenyl-3,6-dihydro-2-oxo-6H-[1,3,4]thiadiazine |
CA2631082C (fr) * | 2005-11-23 | 2015-02-03 | Board Of Regents Of The University Of Texas System | Compose cytotoxique speficique du ras oncogene et ses procedes d'utilisation |
CN101374835B (zh) * | 2006-01-30 | 2012-04-25 | 转化技术制药公司 | 作为PTPase抑制剂的取代的咪唑衍生物、组合物和使用方法 |
WO2007102368A1 (fr) * | 2006-02-28 | 2007-09-13 | Riken | Nouveau dérivé de 3-(1-aminoalkylidène)furann-2,4(3h,5h)-dione, sa méthode de production et une composition pharmaceutique l'incluant au titre de principe actif |
NZ571300A (en) | 2006-04-07 | 2011-12-22 | Warner Chilcott Co Llc | Antibodies that bind human protein tyrosine phosphatase beta (HPTPBeta) and uses thereof |
US20070238700A1 (en) * | 2006-04-10 | 2007-10-11 | Winzenberg Kevin N | N-phenyl-1,1,1-trifluoromethanesulfonamide hydrazone derivative compounds and their usage in controlling parasites |
JP5135588B2 (ja) * | 2006-06-02 | 2013-02-06 | 国立大学法人大阪大学 | 延長型アミロイドβ産生抑制剤 |
US7622593B2 (en) * | 2006-06-27 | 2009-11-24 | The Procter & Gamble Company | Human protein tyrosine phosphatase inhibitors and methods of use |
US7589212B2 (en) * | 2006-06-27 | 2009-09-15 | Procter & Gamble Company | Human protein tyrosine phosphatase inhibitors and methods of use |
CN101506180B (zh) * | 2006-06-27 | 2013-10-30 | 艾尔普罗医疗有限公司 | 人蛋白酪氨酸磷酸酶抑制剂及使用方法 |
US7795444B2 (en) * | 2006-06-27 | 2010-09-14 | Warner Chilcott Company | Human protein tyrosine phosphatase inhibitors and methods of use |
US7838542B2 (en) | 2006-06-29 | 2010-11-23 | Kinex Pharmaceuticals, Llc | Bicyclic compositions and methods for modulating a kinase cascade |
EP2433496A1 (fr) * | 2007-05-08 | 2012-03-28 | Burnham Institute for Medical Research | Inhibiteurs de la phosphatase alcaline non spécifiques aux tissus et leurs utilisations pour le traitement de la calcification des vaisseaux |
CN101828111B (zh) * | 2007-08-21 | 2014-07-23 | 塞诺米克斯公司 | 人t2r苦味受体及其用途 |
WO2009049098A2 (fr) * | 2007-10-09 | 2009-04-16 | Indiana University Research & Technology Corporation | Matériaux et procédés pour réguler l'activité des phosphatases |
AU2008346794A1 (en) * | 2007-12-31 | 2009-07-16 | The Regents Of The University Of California | SERS-based, single step, real-time detection of protein kinase and/or phosphatase activity |
US7786171B2 (en) | 2008-04-04 | 2010-08-31 | Abbott Laboratories | Amide derivatives as positive allosteric modulators and methods of use thereof |
WO2010105243A1 (fr) | 2009-03-13 | 2010-09-16 | Agios Pharmaceuticals, Inc. | Procédés et compositions pour des troubles liés à la prolifération cellulaire |
US8785450B2 (en) | 2009-06-29 | 2014-07-22 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
US8883832B2 (en) | 2009-07-06 | 2014-11-11 | Aerpio Therapeutics Inc. | Compounds, compositions, and methods for preventing metastasis of cancer cells |
DK2451279T3 (da) | 2009-07-06 | 2019-05-20 | Aerpio Therapeutics Inc | Benzosulfonamid derivater forbindelser deraf og deres brug til at forhindre metastaser af cancerceller |
US20120231014A1 (en) * | 2009-08-18 | 2012-09-13 | Case Western Reserve University | Neural Regeneration |
CA2793836C (fr) | 2009-10-21 | 2020-03-24 | Agios Pharmaceuticals, Inc. | Procedes et compositions pour troubles associes a la proliferation cellulaire |
EP3561077B1 (fr) | 2009-10-21 | 2022-12-21 | Les Laboratoires Servier | Procédés pour des troubles liés à la prolifération cellulaire |
JP2013508318A (ja) * | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたベンゾスルホンアミド誘導体 |
KR20130028058A (ko) | 2010-02-03 | 2013-03-18 | 엠이에이치 어소시에이츠, 인코포레이티드 | 선택적 및 생활성 동배체로서의 다수 치환된 플루오로메탄류 |
JP6081354B2 (ja) * | 2010-07-16 | 2017-02-15 | アジオス ファーマシューティカルズ, インコーポレイテッド | 治療活性組成物およびそれらの使用方法 |
CA2810038A1 (fr) | 2010-09-03 | 2012-03-08 | Forma Tm, Llc | Nouveaux composes et compositions pour l'inhibition de nampt |
WO2012112953A2 (fr) | 2011-02-18 | 2012-08-23 | President And Fellows Of Harvard College | Commutateur moléculaire pour la croissance neuronale |
PL3406251T3 (pl) | 2011-05-03 | 2024-04-29 | Agios Pharmaceuticals, Inc. | Aktywatory kinazy pirogronianowej do stosowania w terapii |
CN102827170A (zh) | 2011-06-17 | 2012-12-19 | 安吉奥斯医药品有限公司 | 治疗活性组合物和它们的使用方法 |
CN102827073A (zh) | 2011-06-17 | 2012-12-19 | 安吉奥斯医药品有限公司 | 治疗活性组合物和它们的使用方法 |
SI2800743T1 (en) | 2012-01-06 | 2018-08-31 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and methods for their use |
US9474779B2 (en) | 2012-01-19 | 2016-10-25 | Agios Pharmaceuticals, Inc. | Therapeutically active compositions and their methods of use |
US10786541B2 (en) | 2012-04-09 | 2020-09-29 | Case Western Reserve University | Compositions and methods for treating heart disease and/or injury |
US10206967B2 (en) | 2012-04-09 | 2019-02-19 | Case Western Reserve University | Compositions and methods for treating heart disease and/or injury |
JP6268164B2 (ja) * | 2012-04-09 | 2018-01-24 | ケース ウエスタン リザーブ ユニバーシティ | Larファミリーホスファターゼの活性を阻害する組成物及び方法 |
US10729777B2 (en) | 2012-04-09 | 2020-08-04 | Case Western Reserve University | Compositions and methods for inhibiting the activity of LAR family phosphatases |
WO2014062511A1 (fr) | 2012-10-15 | 2014-04-24 | Agios Pharmaceuticals, Inc. | Composés et compositions thérapeutiques |
EP3019480B1 (fr) | 2013-07-11 | 2020-05-06 | Agios Pharmaceuticals, Inc. | Composés 2,4- ou 4,6-diaminopyrimidine comme inhibiteurs d'idh2 mutantes pour le traitement du cancer |
WO2015003355A2 (fr) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Composés thérapeutiquement actifs et leurs méthodes d'utilisation |
WO2015003360A2 (fr) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Composés thérapeutiquement actifs et leurs méthodes d'utilisation |
US9579324B2 (en) | 2013-07-11 | 2017-02-28 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
US20150031627A1 (en) | 2013-07-25 | 2015-01-29 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
CN110372550B (zh) | 2013-09-09 | 2021-08-24 | 佩洛通治疗公司 | 芳基醚及其用途 |
EP3083639B1 (fr) | 2013-12-16 | 2019-05-29 | Peloton Therapeutics, Inc. | Analogues de sulfone cyclique et de sulfoximine et leurs utilisations |
KR102400737B1 (ko) | 2014-03-14 | 2022-05-20 | 아지오스 파마슈티컬스 아이엔씨. | 치료적으로 활성인 화합물의 약제학적 조성물 |
US10258672B2 (en) | 2014-10-09 | 2019-04-16 | Case Western Reserve University | Compositions and methods of treating root avulsion injury |
US10278942B2 (en) | 2015-03-11 | 2019-05-07 | Peloton Therapeutics, Inc. | Compositions for use in treating pulmonary arterial hypertension |
WO2016144825A1 (fr) | 2015-03-11 | 2016-09-15 | Peloton Therapeutics, Inc. | Composés aromatiques, leurs et utilisations |
WO2016145045A1 (fr) | 2015-03-11 | 2016-09-15 | Peloton Therapeutics, Inc. | Compositions s'utilisant dans le traitement du glioblastome |
EP3268362B1 (fr) | 2015-03-11 | 2021-10-20 | Peloton Therapeutics, Inc. | Pyridines substituées et leurs utilisations |
WO2016168510A1 (fr) | 2015-04-17 | 2016-10-20 | Peloton Therapeutics, Inc. | Thérapie combinée avec un inhibiteur de hif-2-alpha et un agent immunothérapeutique, et applications corresponantes |
WO2016201227A1 (fr) | 2015-06-11 | 2016-12-15 | Agios Pharmaceuticals, Inc. | Procédés d'utilisation d'activateurs de la pyruvate kinase |
US9796697B2 (en) | 2015-06-12 | 2017-10-24 | Peloton Therapeutics, Inc. | Tricyclic inhibitors of HIF-2-alpha and uses thereof |
MD3362066T2 (ro) | 2015-10-15 | 2022-08-31 | Les Laboratoires Servier Sas | Terapie combinată pentru tratamentul tumorilor maligne |
EP4403173A3 (fr) | 2015-10-15 | 2024-10-09 | Les Laboratoires Servier | Polythérapie pour le traitement de tumeurs malignes |
JP6916279B2 (ja) | 2016-07-12 | 2021-08-11 | レヴォリューション・メディスンズ,インコーポレイテッド | アロステリックshp2阻害剤としての2,5−二置換3−メチルピラジンおよび2,5,6−三置換3−メチルピラジン |
TWI739860B (zh) * | 2016-07-18 | 2021-09-21 | 日商日本歐愛特農業科技股份有限公司 | 新穎苯甲醯胺化合物、其製造方法及殺蟎劑 |
CN109476482B (zh) * | 2016-08-19 | 2022-02-18 | 日本曹达株式会社 | 含氟磺酰胺化合物的制造方法 |
CN106645723A (zh) * | 2016-11-04 | 2017-05-10 | 中国人民解放军第二军医大学 | Shp2蛋白在制备肝癌对索拉菲尼疗效评估试剂盒中的应用 |
WO2018136265A1 (fr) * | 2017-01-23 | 2018-07-26 | Revolution Medicines, Inc. | Composés bicycliques utilisés en tant qu'inhibiteurs allostériques de shp2 |
EP4230623A3 (fr) | 2017-01-23 | 2023-10-11 | Revolution Medicines, Inc. | Composés de pyridine en tant qu'inhibiteurs allostériques de shp2 |
EP3678703A1 (fr) | 2017-09-07 | 2020-07-15 | Revolution Medicines, Inc. | Compositions d'inhibiteur de la shp2 et méthodes de traitement du cancer |
CA3078565A1 (fr) | 2017-10-12 | 2019-04-18 | Revolution Medicines, Inc. | Pyridine, pyrazine et composes de triazine utilises en tant qu'inhibiteurs allosteriques de shp2 |
EP3724189B1 (fr) | 2017-12-15 | 2023-10-04 | Revolution Medicines, Inc. | Composés polycycliques comme inhibiteurs allosteriques de la shp2 |
MX2020011405A (es) * | 2018-05-03 | 2021-01-08 | Jiangsu Hengrui Medicine Co | Derivados de bencimidazol como moduladores del receptor gamma huerfano (rory) relacionado con retinoide y usos farmaceuticos de los mismos. |
US10980788B2 (en) | 2018-06-08 | 2021-04-20 | Agios Pharmaceuticals, Inc. | Therapy for treating malignancies |
AU2020377114A1 (en) * | 2019-10-31 | 2022-06-16 | Jiangsu Hengrui Medicine Co., Ltd. | Acid addition salt of RORγ regulator |
CN112745268B (zh) * | 2019-10-31 | 2022-09-16 | 江苏恒瑞医药股份有限公司 | 苯并咪唑衍生物的晶型及制备方法 |
US20230210964A1 (en) * | 2020-06-07 | 2023-07-06 | Sundaram Ramasamy | Compositions and methods for detoxifying bacterial endotoxins and hydrogen sulfide by recombinant fusion enzymes |
CN115637189B (zh) * | 2022-11-14 | 2023-08-29 | 俄美达(武汉)有限公司 | 一种基于多孔性碳材的镁合金切削液的制备方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE758241A (fr) * | 1969-11-03 | 1971-04-30 | Agfa Gevaert Nv | Bereiding van 2-alkyl-thiazolen en 2-alkyl-selenazolen met een geanelleerde aromatische ring |
US4177057A (en) * | 1977-10-25 | 1979-12-04 | United States Borax & Chemical Corporation | Herbicidal benzimidazoles |
US5710173A (en) * | 1995-06-07 | 1998-01-20 | Sugen, Inc. | Thienyl compounds for inhibition of cell proliferative disorders |
WO1998056376A1 (fr) * | 1997-06-13 | 1998-12-17 | Sugen, Inc. | Nouveaux composes heteroaryle pour la modulation de la transduction de signaux cellulaires associee aux enzymes proteine tyrosine |
-
2000
- 2000-08-25 AT AT00961360T patent/ATE309207T1/de not_active IP Right Cessation
- 2000-08-25 CA CA002382789A patent/CA2382789A1/fr not_active Abandoned
- 2000-08-25 EP EP00961360A patent/EP1212296B9/fr not_active Expired - Lifetime
- 2000-08-25 ES ES00961360T patent/ES2252058T3/es not_active Expired - Lifetime
- 2000-08-25 WO PCT/US2000/023293 patent/WO2001016097A1/fr active IP Right Grant
- 2000-08-25 NZ NZ517426A patent/NZ517426A/en unknown
- 2000-08-25 IL IL14824300A patent/IL148243A0/xx unknown
- 2000-08-25 AU AU73321/00A patent/AU775625B2/en not_active Ceased
- 2000-08-25 DE DE60023920T patent/DE60023920T2/de not_active Expired - Fee Related
- 2000-08-25 US US09/645,879 patent/US6596772B1/en not_active Expired - Fee Related
- 2000-08-25 JP JP2001519667A patent/JP2003508382A/ja not_active Withdrawn
-
2002
- 2002-02-26 ZA ZA200201609A patent/ZA200201609B/en unknown
-
2003
- 2003-07-14 US US10/618,083 patent/US20040138255A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU7332100A (en) | 2001-03-26 |
DE60023920T2 (de) | 2006-07-20 |
ES2252058T3 (es) | 2006-05-16 |
ATE309207T1 (de) | 2005-11-15 |
ZA200201609B (en) | 2003-07-30 |
AU775625B2 (en) | 2004-08-05 |
JP2003508382A (ja) | 2003-03-04 |
US20040138255A1 (en) | 2004-07-15 |
CA2382789A1 (fr) | 2001-03-08 |
US6596772B1 (en) | 2003-07-22 |
EP1212296A1 (fr) | 2002-06-12 |
WO2001016097A1 (fr) | 2001-03-08 |
IL148243A0 (en) | 2002-09-12 |
EP1212296B9 (fr) | 2006-05-10 |
DE60023920D1 (de) | 2005-12-15 |
EP1212296B1 (fr) | 2005-11-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1212296B1 (fr) | Mimetiques phosphates et procedes de traitement utilisant des inhibiteurs de phosphatase | |
US5798374A (en) | Methods of inhibiting phosphatase activity and treatment of disorders associated therewith | |
US5935993A (en) | Tyrphostin like compounds | |
CA2293400A1 (fr) | Nouveaux composes heteroaryle pour la modulation de la transduction de signaux cellulaires associee aux enzymes proteine tyrosine | |
US5886195A (en) | Thienyl compounds for inhibition of cell proliferative disorders | |
US5773459A (en) | Urea- and thiourea-type compounds | |
JP5506386B2 (ja) | P53活性化化合物 | |
US6225346B1 (en) | Tyrphostin like compounds | |
US20050038248A1 (en) | Chemotherapeutic agents | |
NZ517451A (en) | Benzophenones as inhibitors of reverse transcriptase | |
CA2222545A1 (fr) | Quinazolines et compositions pharmaceutiques | |
US6316479B1 (en) | Isoxazole-4-carboxamide compounds active against protein tryosine kinase related disorders | |
MX2007007433A (es) | Nuevos derivados de ciclohexano. | |
MXPA06013338A (es) | Tiofen-heteroaril-aminas. | |
WO1996040113A2 (fr) | Inhibiteurs de la phosphatase | |
EP2616450B1 (fr) | Nouveaux composés | |
EP4121411A1 (fr) | Activateurs nucléotidiques non cycliques sélectifs pour le capteur de camp epac 1 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PSEA | Patent sealed | ||
RENW | Renewal (renewal fees accepted) |